Glycosylation orchestrates virulence and pathogenicity of periodontal keystone pathogens

Periodontal diseases, chronic inflammatory conditions initiated by dysbiotic microbial communities, are predominantly driven by the "red complex" pathogens. This review explores how glycosylation on surface molecules of Tannerella forsythia, Porphyromonas gingivalis, and Treponema denticola modulate their pathogenesis. Research reveal glycosylation profoundly impacts synthesis, stability and functionality of major virulence factors like gingipains, fimbriae and surface layer proteins in these keystone pathogens. Distinct glycan motifs facilitate immune evasion by masking antigenic epitopes, subverting immune recognition and skewing inflammatory responses. Remarkably, glycosylation signatures influence crucial virulence traits such as biofilm formation, host adhesion and invasion, potentiating persistence. Through evaluating current literature, this review unravels the interplay between glycosylation pathways and virulence expression, elucidating mechanisms underpinning glycan-mediated host-pathogen interactions and pathology progression. Emerging prospects of exploiting glycosylation as a diagnostic, therapeutic target and vaccine candidate are discussed. Synthesizing cutting-edge findings, this comprehensive review illuminates glycosylation's central role in periodontal pathogenesis.